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Benefits of Human Milk Oligosaccharides on immune-dependent Diseases

At birth, babies’ immune system is not as strong as that of adults; it is still developing, which make the infants susceptible to immune-dependent diseases, such as allergies.1,2 Human breast milk is nature's most perfect source of nutrition providing all the necessary nutrients for babies’ healthy growth and development.3-6 Breastfeeding has several established benefits on child health, including immune-dependent benefits.3,7 Hence, breast milk plays a vital role in the development of mature immune responses during early life.8-10 Among the many different elements of human breast milk, human milk oligosaccharides (HMOs) are the third largest solid component.11,12 HMOs are synthesised by the mammary gland, with mean levels between 10 and 15 g/L in mature human breast milk.11,12

HMOs provide unique immune benefits to the baby.11,13,14 HMOs directly modulate gut mucosal immunity.11,15 In an experimental study, 2'-fucosyllactose (2’FL) and 6'-sialyllactose (6’SL) modulated human epithelial cell responses that were associated with allergic disease.16 HMOs may also have direct effects on systemic immunity,11 as a small part of HMOs reach systemic circulation.17Furthermore, HMOs indirectly support immunity by shaping the developing gut microbiota of infants,11,18 which has become an important aspect of human health.8,19-21 Clinical studies suggest that disturbances in the intestinal microbiota early in life, caused by caesarean delivery or early antibiotic exposure, contribute to the development of immune-mediated diseases, such as allergies or type 1 and 2 diabetes.8,20,22,23 In preclinical studies, the oral use of 2’FL significantly reduced food allergy symptoms,24 and providing HMOs has shown to delay or prevent the onset of type 1 diabetes.25

First promising evidence from observational clinical studies point towards a role of HMOs in immune-dependent diseases, such as atopic dermatitis or food allergy.26-28 Infants at risk of allergies, who were born by caesarean section, had a delayed onset of immunoglobulin (Ig) E-mediated eczema when fed human milk with higher levels of 2’-fucosylated HMOs, such as 2’FL.26 In another cohort study, infants who received human milk with low lacto-N-fucopentaose (LNFP) III levels were more likely to experience cow's milk allergy compared to those who received high LNFP III-containing milk.27 In a subgroup of a another cohort study, a certain profile of 10 HMOs in human breast milk, rather than individual or total HMOs, was associated with food sensitisation in the first year of life.28

Professor Hania Szajewska, Department of Paediatrics of the Medical University of Warsaw, Poland

Presented data suggest that the specific HMO profile in mother’s milk may help to reduce food sensitisation in her baby. Although food sensitisation is not necessarily a proof of an allergy, it may be considered as an important clinical indicator and predictor of future allergic disease. The exact mechanism how specific HMOs may help reduce the risk of allergy remains to be explored. Among the many ways how HMOs can influence immunity, HMOs contribute to the development of healthy gut microbiota, by acting as prebiotics. Alterations in the gut microbiota (dysbiosis) is known to play a role in allergy diseases. So far, no individual HMO has been associated with food sensitisation; however, it is likely that not all HMOs are equal.

Another interesting finding is the effect observed in children born by caesarean section. The rate of caesarean sections is increasing both in developed and developing countries. Recent studies confirm different colonisation patterns in infants born by caesarean delivery compared with infants born by vaginal delivery, which may persist beyond infancy. The exact effects of those differences on children’s health are still to be evaluated. Yet, evidence exists that it may increase the risk of specific diseases, including allergy.


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